A combined theoretical and experimental approach to the study of metabolic channeling

细胞代谢是将代谢物转化为生命所需分子的一系列酶促反应和运输过程。通常，酶在功能途径的背景下作为一个集体系统运作。最近的研究表明，这些途径通过形成亚细胞区室或蛋白质复合物表现出高度的空间组织。这种组织提供了一种机制，将底物从一种酶“引导”到另一种酶，从而提高了产物收率和反应效率。通过通道内的空间协调酶，有机会将通道的潜在好处转化为代谢工程目前针对的许多应用。在一种将生物信息学与计算机模拟相结合的新颖多学科方法中，我们建议系统地确定通道运行和改善通路性能所需的条件。通过预测最可能受益于通道的反应，这些知识将被用于更有效地设计合成途径。

Cellular metabolism represents a collection of enzymatic reactions and transport processes that convert metabolites into the molecules required for life. Typically enzymes operate as a collective system within the context of functional pathways. Recent studies have revealed that these pathways exhibit a high degree of spatial organization either through the formation of sub-cellular compartments or protein complexes. Such organization provides a mechanism to 'channel' a substrate from one enzyme to another, increasing product yield and reaction efficiency. Through spatially coordinating enzymes within pathways, there is an opportunity to translate the potential benefits of channeling to many applications currently being targeted by metabolic engineering. In a novel and multi-disciplinary approach combining bioinformatics with computer simulations, we propose to systematically identify the conditions required for channeling to operate and improve pathway performance. By predicting reactions which are most likely to benefit from channeling, this knowledge will be exploited to design synthetic pathways more effectively.